Obesity is a serious and growing public health problem in the United States and the world. While many overweight and obese individuals can lose weight, few can maintain weight loss for substantial periods of time. This suggests that physiological adaptations occur with weight loss that oppose further weight loss and promote weight regain. The weight reduced state is associated with alterations in meal-related hormone responses as well as long-term adiposity signals such as leptin both potentially promoting increased energy intake. While these signals may directly impact energy balance regulation, there is increasing evidence that these physiologic signals interact with reward, behavioral and cognitive systems to ultimately enhance food intake. For example, in normal weight individuals, there appear to be important interactions between environmental food-related cues and brain regions known to be important in the homeostatic regulation of food intake, and these interactions are affected by food intake and energy balance. These responses appear to be altered in obesity and more so following diet-induced weight loss which would favor increase food intake. This inability to properly adapt to the environment may represent an important mechanism for the difficulty of successful long-term weight loss maintenance. Successful weight loss maintenance interventions must, therefore, require control of energy balance via a complex interaction between physiologic and nonphysiologic systems, and understanding these mechanisms will allow for the potential development of new and/or better strategies for weight loss maintenance. Two such successful interventions are weight loss surgery and exercise. While both of these interventions have been shown to been associated with changes or 'normalization'in meal-related hormone responses that might favor reduced food intake, the mechanisms by which these interventions help promote weight loss and prevent weight regain are not well understood. Studies designed to elucidate the mechanisms of successful weight loss maintenance interventions such as these are a critical area for investigation. The overall goal of this proposal is to examine the effects of weight loss surgery and exercise on the neuronal, behavioral and hormonal response to a meal. It is hypothesized that these successful weight loss maintenance interventions will restore the normal neuronal response to a meal and that this improved neuronal response will be associated with changes in both meal associated hormones and appetite ratings. In order to examine these hypotheses we propose to use fMRI to examine the neuronal response to visual food cues before and after a meal as well as to study the hormonal response to a meal in individuals who have undergone Roux-en-Y gastric bypass or gastric banding as compared to diet control and in individuals maintaining weight loss through a supervised exercise intervention as compared to diet control. PUBLIC HEALTH RELEVANCE: Obesity is a serious and growing public health problem in the United States and the world. While many overweight and obese individuals can lose weight, few can maintain weight loss for substantial periods of time. This suggests that adaptations occur with weight loss that oppose further weight loss and promote weight regain. The most successful interventions for sustained weight loss are bariatric surgery and exercise. It is unclear, however, how these interventions help individuals maintain a reduced body weight. By understanding the complex interactions between the brain response to eating and food cues and physiologic changes with these interventions we hope to be able to develop new strategies and/or interventions for sustained weight loss.